Evidence map›Paper›PMID 40603872›Full record

ArticleNature communications2025

Pol θ-mediated end-joining uses microhomologies containing mismatches.

Yuzhen Li, Ngoc K Dang, Wei He, Mark Returan, Denisse Carvajal-Maldonado, Adele T Guerin, Han Xu, Bin Liu, Richard D Wood

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  2. Dynamic Assemblies in Genome Maintenance.Advances in experimental medicine and biology · 2026
    Review
  3. Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yuzhen LiDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4068-8316
Ngoc K DangDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.
Wei HeDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-3088-5650
Mark ReturanDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.
Denisse Carvajal-MaldonadoDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9318-1207
Adele T GuerinDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0009-0006-2838-4044
Han XuDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8654-461X
Bin LiuDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9113-9694
Richard D WoodDepartment of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, USA. rwood@mdanderson.org.ORCID http://orcid.org/0000-0002-9495-6892

Funding

Structural determinants of Pol theta functionP01CA247773 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DALE A RAMSDEN · 2020 to 2026
$15.2M
Computational approaches for protein functional analysis using CRISPR screensR35GM137927 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI XU, HAN · 2020 to 2024
$2.0M
NCI NIH HHS P01 CA247773NIGMS NIH HHS R35 GM137927U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA247773U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM137927
6 · The paper itself

Abstract

DNA polymerase theta (Pol θ) initiates repair of DNA double-strand breaks by pairing single strands at short "microhomologies". It is important to understand microhomology selection, as some cancer cells rely on Pol θ for survival. Here, we investigate end-joining by purified human Pol θ, employing DNA sequencing of products generated from oligonucleotide libraries having diverse 3' ends. Pol θ overwhelmingly selects short internal microhomologies found within 15 nucleotides of the terminus of single-stranded DNAs, restricting deletion size during end-joining. Significantly, we find that the selected microhomologies are usually interrupted by mismatches and that base pairing within 6 nucleotides of the 3' end is important for determining microhomology choice. Bidirectional synthesis is not necessary to initiate end-joining. The preference for mismatched microhomologies suggests a revision of the definition of microhomology to account for the unique properties of Pol θ. This could advance the analysis of mutations in cancer genomes.

Indexed as

Base Pair MismatchDNA-Directed DNA PolymeraseDNA End-Joining RepairDNA Breaks, Double-StrandedDNA Polymerase thetaDNA, Single-StrandedHumansDNA-Directed DNA PolymeraseDNA Polymerase thetaDNA, Single-Stranded

Identifiers

PMID40603872
PMCPMC12222517

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.